This application relates to an interdisciplinary center in human and medical genetics and inherited diseases. The aim of the program is understanding of gene action in man with particular reference to ultimate prevention and treatment of genetic diseases. Particular emphasis in many projects is given to the interaction of heredity and environment in the pathogenesis of common disease. The Center brings together investigators whose interests range from basic to clinical approaches. Methods used in the various studies involve some aspects of DNA technology, enzyme and protein biochemistry, genetic tumor tracing techniques, cytogenetics, tissue culture, gene cloning, observation of natural history of disease, as well as family and population studies. Most investigations are done on human blood and tissue but yeast and mice are also used. Several core units serve as general resources while specific research projects include 1) cloning of human genes in yeast; 2) mechanisms of mammalian X chromosome inactivation; 3) mechanisms and detection of human hemoglobin mutations in vitro; 4) biochemical and genetic studies on a) traits of pharmacogenetic and ecogenetic significance (paraoxonase, transketolase, aryl hydrocarbon hydroxylase), and b) mekbrane defect(s) in hypertension; 5) tumor genetics in mice as models for oncogenesis in man; and 6) mechanisms and natural history of Turner syndrome.